Skin hyperpigmentation has been directly related to the formation of melanin, a dark pigment formed via tyrosine. The initial steps in tyrosine to melanin conversion are mediated by the enzyme tyrosinase. Effective tyrosinase inhibitors may inhibit melanin formation and are used to reduce undesirable skin pigmentation (e.g. skin brightening and/or evening out skin tone and/or reducing the appearance of age spots). Currently, several tyrosinase inhibitors are used in the marketplace and include hydroquinone, kojic acid and arbutin. However, these products have various disadvantages; for example, kojic acid displays low bioavailability and thereby affords marginal efficacy.
A fungal metabolic product, kojic acid has been commonly used as a skin brightening ingredient. Kojic acid has been shown to be safe and effective for topical use (see review by Burdock et al., 2001, Regulatory Toxicology and Pharmacology 33: 80-101). Kojic acid monoesters and diesters have been described (Nagai, S.; Izumi, T., U.S. Pat. No. 4,369,174); they appear to have excellent tyrosinase-inhibiting activity so as to inhibit skin melanin formation. This inhibition can produce excellent effects in skin brightening.
Kojic acid halogenation (i.e. chloro-kojic acid, bromo-kojic acid, etc.) and subsequent reduction to afford allomaltol (5-hydroxy-2-methyl-4H-pyran-4-one) has been previously described (for example, Liu, Z. D. et al, Bioorg. Med. Chem. 2001, 9, 563-573). Furthermore, 5-hydroxy-2-methyl-4H-pyran-4-one has been described as a treatment for pigmentation disorders (Yamamoto, S. JP Patent 04036217), sunburn prevention (Sansei Pharmaceutical Co., JP Patent 57134409), and as an antioxidant for oils and fats (Sansei Pharmaceutical Co., JP Patent 57137394). Hence, compositions based on esters of 5-hydroxy-2-methyl-4H-pyran-4-one may reduce melanin formation and enhance the potential to provide a noticeable brightening benefit with decreased skin irritation. Other likely benefits for these esters may include the potential for sunburn prevention and usage as novel antioxidants. It is the object of this invention to provide such compounds and compositions.